Abstract 2897: Therapeutic efficacy of antibodies targeting domain 1 of HSPG2 in breast cancer

Abstract

Abstract Significant advancements in chemotherapy have improved the survival rates of patients presenting with local or regional breast cancer to as high as 99% and 85%, respectively. On the contrary, patients with metastatic breast cancer have a dismal 5-year survival rate of 26%. Thus, there is an urgent need for research strategies directed towards treatment of metastasis. Our lab used a phage display-based cell panning procedure to develop two fully humanized antibodies (Clone 6 and AM6) that are able to bind specifically to breast cancer metastatic cells. Target deconvolution revealed HSPG2/Perlecan Domain 1 as the cell surface antigen bound by the antibodies. Immunohistochemistry studies revealed high HSPG2 expression across various tumor subtypes including melanoma, bladder cancer, glioblastoma and ovarian cancer. There was a significant correlation between high HSPG2 and with poor survival in bladder and ovarian cancers. Interestingly, we observed significant tumor growth inhibition in the triple-negative MDA-MB-231 breast cancer xenograft model. This efficacy was significantly reduced when the tumor growth inhibition studies were repeated in NSG mice, suggesting NK cell-mediated antibody dependent cellular cytotoxicity (ADCC) as the potential mechanism of action. The data presented here point to the relevance of HSPG2 as a novel target for not only breast cancer but also other malignancies. We also show the potential of Clone 6 and AM6 as therapeutic and targeting agents. Further studies are required to understand the significance of HSPG2 overexpression and its correlation with tumor progression as well as to confirm the mechanism of action with Clone 6 and AM6 antibodies. Citation Format: Vidhi Khanna, Stephen Kalscheuer, Jayanth Panyam, Da Yang, Sihan Li. Therapeutic efficacy of antibodies targeting domain 1 of HSPG2 in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2897.